University of Illinois Cancer Center member Larisa Nonn has received a three-year grant from the U.S. Department of Defense to conduct research to determine whether the lack of vitamin D in African American men increases the amount of testosterone and estrogen within the prostate, leading to a higher risk of cancer.
“Although the disparity of vitamin D deficiency in African Americans is well known, the clinical significance is often questioned because African American men do not have soft bones, which is a classic symptom of vitamin D deficiency,” said Nonn, PhD, associate professor of pathology in the University of Illinois College of Medicine. “If clinicians are aware of a direct mechanism by which these men are increasing their risk of prostate cancer, they would strongly recommend taking a vitamin D supplement.” For more information watch this video.
The pigment melanin reduces the capacity to produce vitamin D, Nonn said, and is the main reason for its deficiency in African American men. Vitamin D is not actually a vitamin, but a hormone, as it is synthesized in the skin following sun exposure. African American men are disproportionately low in vitamin D compared to those of European descent, with 90 percent of African American men being vitamin D deficient.
Not only are African American men at an increased risk of contracting prostate cancer, but they also get it at a younger age and it is more lethal, Nonn said. The disparity in prostate cancer in African American men is likely due to multiple contributors, one of which may be vitamin D. Vitamin D works in the body similar to that of testosterone and estrogen, although each hormone has distinct functions.
“Our studies have shown that men with low vitamin D status opens an “entryway” into prostate tissue to let in more vitamin D, but we only observed this in African American men,” Nonn said. The entrance, known as megalin, is also responsible for allowing testosterone and estrogen into cells. In the prostate, high levels of testosterone and estrogen are known drivers of prostate cancer, she said.
Nonn will use samples from patients’ stored blood, prostate tissue and tissue from fresh prostate cells to perform the studies. Should she discover the link between vitamin D deficiency and the change in tissue levels of hormones, it could be applicable to other cancers, she said.
“Megalin is also present in breast cancer, and there is a pronounced breast cancer disparity for African American women,” she said. “Intervention and adequate vitamin D supplementation from a young age may ultimately not only reduce prostate cancer mortality, but also other cancers and disease.”
Nonn’s grant runs for three years and is her third Department of Defense funded project as a UIC faculty member. She previously received one of the grants as a postdoctoral fellow at Stanford University. She will be assisted by UI Cancer Center member Gail Prins, PhD, Michael Reese Professor of Urology and Physiology in the UI College of Medicine, and Bethany Baumann, PhD, postdoctoral fellow.
Nonn is not the sole researcher in her laboratory who has received a grant to study prostate cancer in African American men. Zachary Richards recently obtained a National Research Service Award Individual Predoctoral Fellowship (F31) from the National Institutes of Health to research the correlation.
Richards, a graduate student and PhD candidate, will seek to explain the differences in the mechanism of cellular uptake and metabolism of vitamin D in primary prostate cells from African American and Caucasian men, and define the role of megalin in endocytosis of vitamin D and testosterone in the prostate. This is his first federally funded research project.
In his previous work, Richards compared the differences in vitamin D metabolite levels between the serum and prostate tissue in a group of prostate cancer patients from different ethnicities. The results were the precursor to Nonn’s new grant, and it suggested that vitamin D status was “more complex than we previously thought,” he said.
“We found that African American men had lower vitamin D status in the serum, but higher levels of active vitamin D in their prostate tissue compared to Caucasian men,” Richards said.
“Megalin is of particular relevance to the prostate since it also binds the sex-hormone globulin to facilitate androgen import,” Richards said. “This dual role of megalin has not been explored and is of great interest, as it presents a potential mechanism of increased prostatic testosterone in the setting of vitamin D deficiency.”